Benzyl substituted rhodanine derivatives of the general formula ##STR1## wherein R.sup.1, and X are as set forth below, are known to be active in treating inflammation, inflammatory bowel disease (hereinafter IBD), allergies, arthritis, hypoglycemia and muscular dystrophy and in preventing ischemia induced cell damage. For example, U.S. Pat. No. 5,216,002 discloses that certain benzyl-substituted rhodanine derivatives are useful for treating IBD. EPO Publication No. 391644, on the other hand, discloses the effectiveness of such compounds for treating inflammation, arthritis, and muscular dystrophy and for preventing ischemia induced cell damage. EPO Publication No. 343643 describes the use of such compounds for treating allergies and inflammation, while EPO Publication No. 587377 discloses these compounds as being effective in treating hypoglycemia.
All of the above patents and publications describe various processes for making the benzyl-substituted rhodanine derivatives disclosed therein. U.S. Pat. No. 5,216,002, further, describes a process for selectively isolating by kinetic resolution, in substantially pure enantiomeric form, one of the enantiomers of a racemic mixture of a benzyl-substituted rhodanine. The process disclosed therein comprises oxidizing the racemic sulfide compound until the undesired enantiomer of the sulfide substrate has been converted to its sulfoxide analog and then separating the unreacted portion of the sulfide substrate from the reaction mixture.
The current processes for preparing benzyl-substituted rhodanine derivatives, as set forth above, are, in general, satisfactory. However, there is room for improvement in process yield and the product purity obtained therefrom, particularly for compounds which have a stereocenter at the 5-position of the rhodanine ring. The current process for preparing compounds having such stereocenter (as set forth in U.S. Pat. No. 5,216,002) sets the center in the last step of the process which results in a low overall yield of desired product because a substantial amount of the undesired enantiomer must be discarded. Furthermore, the chromatographic purification step required to recover the desired enantiomer is difficult to perform, especially on a production scale. Finally, the process is expensive requiring large amounts of catalyst.
The present invention provides an improved process for preparing benzyl-substituted rhodanine derivatives. The process of the present invention is particularly useful for synthesizing the enantiomers of such derivatives since the chiral center is set at an early stage of the synthesis resulting in a higher overall yield of the desired enantiomer. In addition, the process can be performed with inexpensive, readily available reagents. Other objects, features and advantages of the present invention will become apparent from the subsequent description and the appended claims.